A Vitamin B<sub>9</sub>-based Dietary Supplement Normalizes the Expression of Lipid Metabolism Regulatory Genes in a Mouse Model of a High-cholesterol Diet

Abstract

The Western Diet (WD) is a nutritional style characterized by excessive intake of cholesterol, saturated fatty acids and sugars; this nutritional pattern can cause type 2 diabetes, metabolic syndrome and other disorders, particularly during ageing. The search for effective approaches to managing the metabolic syndrome caused by WD seems to be a relevant research task. Unfortunately, this issue has attracted insufficient attention in the current literature. In this work, we use a mouse model of WD to study potential effects of a food supplement based on dicholine succinate (DS) and folic acid (vitamin B9), which are activators of mitochondrial functions. We study glucose tolerance, parameters of hippocampus-dependent learning and relative gene expression in RT-PCR of molecular markers of negative WD effects in the brain and liver of aging mice housed on WD. Mice C57BL/6 were 12 months old and housed on WD for 3 weeks; some groups received В9 (5 mg/kg/day) or DS (150 mg/kg/day), or their combination, via water. We carried out food displacement and fear conditioning learning tests followed by RT-PCR of several genes in the liver and brain. We found a decreased glucose tolerance, an elevated speed of pellet displacement and a reduction of freezing time in the fear conditioning test. This may suggest cognitive deficits and impulsivity of mice housed on WD. The administration of DS and B diminished most of these changes. In addition, the increased expression of FASN in the liver points to new mechanisms of negative WD effects during aging. The food supplement based on B9 and DS normalizes FASN expression and behavior, as well as glucose tolerance in WD-housed mice. Our results open new perspectives for further studies of therapeutic and preventive effects of food supplements on the regulation of metabolic parameters during ageing.